BMP-2 variants with improved properties

Abstract

The invention relates to variants of BMP-2 with improved properties and methods for their use.

1 - 27 . (canceled)  
     
     
         28 . A non-naturally occuring variant BMP-2 protein comprising at least one substitution as compared to an amino acid sequence comprising SEQ ID NO:1, said substitution selected from the group consisting of: S12E, S13K, K15D, P18R, P18T, S24N, S24Q, N29D, N29S, W31A, W31E, W31N, W31Q, P36K, P36Q, P36R, P36S, P36T, H39E, H39Q, F41D, F41N, E46Q, D53Q, D53T, Q64E, L66E, L66N, L66Q, S69A, S69D, S69R, S69F, V70E, V70K, V70Q, V70T, N71K, S72D, S85E, A86D, L90E, L90K, Y91D, Y91E, Y91K, Y91T, N95D, N95S, E96D, E96S, E96N, V98A, V98D, V98R, V98T, L100A, L100E, L100K, L100Q, Y103D, Q104D, and E109R.  
     
     
         29 . A BMP-2 variant protein of  claim 28 , wherein a substitution is K15D.  
     
     
         30 . A BMP-2 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of F41D and F41N.  
     
     
         31 . A BMP-2 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of S69A, S69D, S69R, and S69F.  
     
     
         32 . A BMP-2 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of N95D and N95S.  
     
     
         33 . A nucleic acid encoding the non-naturally occurring variant BMP-2 protein of  claim 28 .  
     
     
         34 . An expression vector comprising the nucleic acid of  claim 33 .  
     
     
         35 . A host cell comprising the nucleic acid of  claim 33 .  
     
     
         36 . A host cell comprising the expression vector of  claim 34 .  
     
     
         37 . A method of producing a non-naturally occurring BMP-2 protein comprising culturing the host cell of  claim 35  under conditions suitable for expression of said nucleic acid.  
     
     
         38 . The method according to  claim 37  further comprising recovering said BMP-2 protein.  
     
     
         39 . A pharmaceutical composition comprising the BMP-2 protein of  claim 28 , and a pharmaceutical carrier.  
     
     
         40 . A method for treating a BMP-2 responsive disorder comprising administering the non-naturally occurring BMP-2 protein of  claim 28  to a patient in need of said treatment.  
     
     
         41 . The method according to  claim 40 , wherein said BMP-2 responsive disorder is selected from the group consisting of bone fractures, bone degeneration and spinal fusion.